In seeking a renewal of our current grant, the following studies, based on our hamster model, are proposed. We will attempt to: (1) indicate the mechanism of pancreatic carcinogenesis through metabolic and alkylation studies (e.g., to ascertain the site and type of alkylation, the consistency of binding), as well as the rate and persistency of repair in target, and non-target tissue in the susceptible (hamster) and resistant (rat) species. In this context, the effect in the two species on pancreatic carcinogenesis of some modifying agents will be sought out. (2) We plan to determine modifying factors in pancreatic carcinogenesis by studying the effect of substances which influence the pancreas function by altering the blood supply and/or the physiologic response of pancreatic cells. (3) We will develop techniques for early detection of induced pancreatic cancer by radioimmunoassay. This study will concentrate on two areas: a) determination of circulating endogenous and exogenous hormones, such as insulin, glucagon, gastrin and glucose (including the tolerance test) during pancreatic carcinogenesis and b) Determination of the relationship between circulating levels of mucin (produced by cancer) and the extent during the tumor development. (4) We will conduct comparative morphologic-epidemiologic studies in human pancreas (random selection of autopsy material; surgical specimens of tissues after total pancreatectomy due to pancreas cancer) with 3 objectives: a) to determine the ultimate pancreatic cancer incidence by screening for occult and microscopic malignant lesions, b) to correlate human pancreatic lesions with those induced in our model and c) to correlate the histologic findings with clinical history with special emphasis on smoking and drinking habits, diabetes, liver and bile duct disease, etc. (5) Finally we will develop therapeutic methods (or induced pancreatic cancer) by using specific substances obtained by bound antibody (to tumor mucin) to specific and potent chemotherapeutic agents.